Three-dimensional Printing of Drug-eluting Implants and Orodispersible Films
Type of DegreePhD Dissertation
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Three-dimensional (3D) printing is a rapidly emerging additive manufacturing technology utilized to quickly fabricate customized dosage forms with complex geometrical designs. Due to its flexibility in adjusting the dose, on-demand manufacturing, cost-effective production, and ability to tailor the drug release profiles, it can greatly lower the adverse effects thereby improving patient compliance. Chapter 1 will discuss the advantages and limitations of different 3D printing technologies in drug delivery. Polymeric dosage forms in contrast to conventional systems can provide optimal targeted release thus lowering the systemic concentrations of drug. 3D printing of such drug delivery systems (drug-eluting metallic implants, polymeric implants, orodispersible films, and patches) allows one to control the release kinetics by changing various printing (infill density, geometry, layer thickness) and process (post-print chemical treatments, drying) parameters. Chapter 2 will cover different 3D printed drug delivery systems along with various 3D printing parameters affecting the release profile. 3D printed 316L stainless steel orthopedic devices were surface modified with multilayer coatings containing a widely utilized NSAID, meloxicam, and a biodegradable polymer poly (lactide-co-glycolic acid) (PLGA). These multilayer depositions provided sustained and targeted delivery, improved the adhesion of osteosarcoma (U2OS) cells to the implant surface, and reduced the bacterial adhesion and biofilm formation of S.aureus and S.pseudintermedius thereby addressing the issues related to implant failure, pain management, and surgical site inflammation. 3D printed polycaprolactone (PCL) implant loaded with anti-obesity drug, capsaicin was fabricated utilizing direct powder extrusion 3D printing technique. Different 3D printing parameters such as iii infill density, printing temperature and pressure were optimized to obtain cylindrical implants. The surface morphology revealed a smooth and uniform external surface with low surface roughness. In vitro release of capsaicin was sustained for more than three months and thus can serve as a long-acting injectable formulation for targeting the adipose tissue region in obese patients. Despite rapid progress in tissue engineering, repair and regeneration of bone defects still remains a challenge, especially for non-homogenous and complicated defects. We have developed biodegradable ketoprofen-eluting porous implantable discs for bone regeneration utilizing direct powder extrusion-based printing technique. The characteristics of the printed discs were evaluated, and the in vitro release of drugs embedded in the porous discs was investigated. It was demonstrated that printing parameters such as infill density, wall thickness, and geometry played an important role in controlling the release and degradation of porous implantable discs. Fast dissolving orodispersible films loaded with sildenafil citrate were fabricated using semisolid/ pneumatic extrusion-based 3D printing technique. Films with different concentrations of hydroxypropyl methylcellulose (HPMC), Pure-Cote® (modified starch) and glycerol were printed, which showed faster disintegration and dissolution. Moreover, by utilizing 3D printing technology, mesh-like films were printed which showed rapid disintegration (20 s) and dissolution (~90% drug released in 4 min) compared to conventional plain films.